A. Field of the Invention
The present invention relates to the treatment of disease or ailments in humans or animals. More particularly, the invention relates to a method and apparatus to deliver surgical or therapeutic compounds such as drugs and genes into cells of human or animal tissues.
B. Description of Related Art
Gene therapy represents a promising modality for the treatment of a variety of acquired and inherited diseases afflicting humans of all ages. The therapy involves the introduction of genes into cells so as to correct for defective genes responsible for the cause of the ailment or disease. There are two approaches to performing gene therapy; ex-vivo and in-vivo. Ex-vivo requires the harvesting of cells, introduction of genes into harvested cells, and subsequent implantation of cells back into the human or animal body. In-vivo gene therapy negates the need to harvest cells since direct injection of genes into tissues is more convenient as a treatment modality. In-vivo gene therapy is desirable since it resembles conventional drug therapy.
There are several methods of gene delivery required in conjunction with in-vivo gene therapy. These methods serve to introduce the desired genes into patient cells. The most promising for high efficiency of gene expression is the use of a viral vector. A viral vector contains the therapeutic gene attached to a key promoter of an attenuated virus. Once introduced into tissue, a viral particle infects a cell lacking the desired gene and subsequently incorporates the therapeutic gene within the genetic system of the cell. But the use of a viral vector introduces issues of toxicity and safety since viral vectors can produce protein products that are allergenic to the patient as well as the possibility of causing uncontrolled growth by random translocation. Therefore the use of non-viral gene delivery methods are more desirable for the future.
Recently it was discovered that direct injection of plasmid DNA into skeletal muscle can be taken up by muscle cells and be expressed in animal cells. Direct injection of genetic material into tissues should alleviate the issues of toxicity and safety in humans but the efficiency of expression of the plasmid DNA is rather low. This is attributable to the low amount of plasmid DNA that actually get transported through cell membranes and subsequently make their way to the nuclei of cells. Thus, there exists the need to enhance transport of genetic materials into intracellular space as well as transport to the vicinity of the nucleus.
Several chemical and physical methods have been applied with direct injection of genes to enhance the efficiency of gene uptake and subsequent expression. The chemical methods range from combining the naked DNA with calcium phosphate precipitate to the use of liposomes and receptor-mediated molecules. The physical methods range from electroporation to biolistic transport.
Electroporation uses brief electrical pulses produced by electrodes in the range of kV/cm to create transient pores in cell membranes located between the electrodes. Biolistic transport is the bombardment of cells or tissues with particles coated with DNA. The particles are accelerated into tissue by devices analogous to guns. The guns generate explosive acceleration by either using very high pressure gases or by electric field discharge. These physical gene delivery methods have demonstrated practical utility for in-vitro transfection of animal and plant cells and limited in-vivo transfection of animal and human tissues.
Although electroporation and biolistics have demonstrated practical gene delivery into tissues, their use on human tissues are limiting by the nature of their means of implementation. Electroporation uses very high voltage potentials and requires that the cells be placed in between the electrodes. Gene delivery into confined spaces such as the inner walls of blood vessels and arteries is problematic due to limited working spaces and relatively delicate nature of the tissues. High voltages placed on the surface of tissues such as skin will produce damage due to excessive heating and dielectric breakdown. Particle acceleration into tissues is limiting by the use of guns requiring high gas pressure and electric discharge to accelerate them. These requirements tend to produce devices, although hand-held, that are relatively large and limit their application to superficial distances from the tissues as well as in confined spaces such as blood vessels or in various cavities of the body such as the lungs. Thus there exists a need for method and device that can effect membrane permeability with relatively less traumatic means as well as providing easy access to confined, or spaces deep within animal and human organs. Ultimately the method and apparatus serve to enhance the uptake and subsequent expression of direct injection gene therapy.
Patents of interest related to the present invention include the patents issued to Sandford et al., U.S. Pat. Nos. 5,487,744, 5,371,015, 5,100,792 and 5,036,006; the patents to Shimada et al., U.S. Pat. No. 4,819,751; Shimada et al., U.S. Pat. No. 5,267,985; Lipkover, U.S. Pat. No. 5,421,816; Shapland et al., U.S. Pat. No. 5,286254; Shaplan et al., U.S. Pat. No. 5,498,238; Eppstein et al., U.S. Pat. No. 5,445,611; the patents to Hoffinann et al., U.S. Pat. Nos. 5,439,330 and 5,507,724; Crandell et al., U.S. Pat. No. 5,304,120 and Miller, Jr., U.S. Pat. No. 5,141,131.